malate-aspartate shuttle parentage

[ValWood]

Although it plays a crucial role in respiration malate-aspartate shuttle is not directly part of the electron transport chain (ETC)

parent should move up to
GO:0045333 cellular respiration

[deustp01]

opinions, @sjm41 ?

[ValWood]

More info. There are 3 children:

so it should apply to one or more of these.

GO:0022904 respiratory electron transport chain
Definition
A process in which a series of electron carriers operate together to transfer electrons from donors such as NADH and FADH2 to any of several different terminal electron acceptors to generate a transmembrane electrochemical gradient.

so I suppose it could fit, but most descriptions of the respiratory ETC begin with mitochondrial NADH.

The problem I see is that in this case the citric acid cycle and other NADH providing systems could be included?

[rozaru]

On a related note:
Could 'malate-aspartate shuttle' term become also a child of NADH oxidation?
The other pathway that does a similar reaction 'glycerolphosphate shuttle' (GO:0006127) is part of NADH oxidation.

[ValWood]

That would definitely be correct, but I wonder if we plan to keep NADH oxidation (seems like a single-step process, so maybe should only be in molecular function @pgaudet ).

Anyway, I will add this parent for consistency.

"Glycerophosphate shuttle" should have some mitochondrial transport parent....

[deustp01]

That would definitely be correct, but I wonder if we plan to keep NADH oxidation

Is NADH oxidation (or NAD reduction) ever annotated in isolation, or always as a part of a larger reaction (process) in which a second participant is reduced or oxidized?

Here, NADH oxidation is conventionally described as part of a process that couples the shuttling of malate and aspartate to oxidation and reduction reactions that collectively result in the transfer of electrons from cytosolic NADH into the mitochondrial membrane where they can enter the electron transport process, with concomitant shuffling of carbon atoms from malate and aspartate - https://en.wikipedia.org/wiki/Malate%E2%80%93aspartate_shuttle

All of this suggests that the discussion here parallels the old one of whether NADH oxidation / reduction or ATP dephosphorylation / phosphorylation are instances of purine metabolism because of the purine component of both molecules.

[ValWood]

These are the only direct EXP annotations to NADH oxidation:

UniProtKB:Q9JXV5 Fructose-1,6-bisphosphate aldolase GO:0006116
UniProtKB:P0DOB5 ATP-dependent 6-phosphofructokinase GO:0006116
UniProtKB:Q9ALA2 NAD(P) transhydrogenase subunit alpha GO:0006116
UniProtKB:Q07637 Pyruvate kinase GO:0006116
UniProtKB:P05062 Fructose-bisphosphate aldolase B GO:0006116
UniProtKB:P08201 Nitrite reductase (NADH) large subunit GO:0006116
MGI:MGI:95679 glycerol-3-phosphate dehydrogenase 1 (soluble) GO:0006116
MGI:MGI:95679 glycerol-3-phosphate dehydrogenase 1 (soluble) GO:0006127
RGD:621381 glycerol-3-phosphate dehydrogenase 1 GO:0006116
FB:FBgn0022160 Glycerophosphate oxidase 1 GO:0006127
FB:FBgn0001098 Glutamate dehydrogenase GO:0006116
UniProtKB:P0DMQ6 Sorbitol dehydrogenase GO:0006116
SGD:S000001417 Mitochondrial glycerol-3-phosphate dehydrogenase GO:0006116
AGI_LocusCode:AT3G10370 SUGAR-DEPENDENT 6 GO:0006127
SGD:S000002243 Mitochondrial external NADH dehydrogenase GO:0006116
SGD:S000002180 NAD-dependent glycerol-3-phosphate dehydrogenase GO:0006116
RGD:1311112 phosphoenolpyruvate carboxykinase 2 (mitochondrial) GO:0006116
RGD:1311112 phosphoenolpyruvate carboxykinase 2 (mitochondrial) GO:0006116
RGD:2503 NAD(P)H quinone dehydrogenase 1 GO:0006116
SGD:S000000349 Alcohol dehydrogenase isoenzyme V GO:0006116
SGD:S000004589 NADH:ubiquinone oxidoreductase GO:0006116
SGD:S000004918 Glucose-repressible alcohol dehydrogenase II GO:0006116
SGD:S000005446 Alcohol dehydrogenase GO:0006116
SGD:S000005446 Alcohol dehydrogenase GO:0006116
SGD:S000005446 Alcohol dehydrogenase GO:0006116
SGD:S000005420 NAD-dependent glycerol 3-phosphate dehydrogenase GO:0006116
SGD:S000004753 Mitochondrial external NADH dehydrogenase GO:0006116
SGD:S000004688 Mitochondrial alcohol dehydrogenase isozyme III GO:0006116

[pgaudet]

Hi @deustp01
In the wiki page you cite, 'NADH oxidation' is also described as 'NAD regeneration' (specifically, the authors write "Since the malate–aspartate shuttle regenerates NADH inside the mitochondrial matrix"). We also have a GO term for NADH regeneration; would that not be a more appropriate description of the biological purpose of the malate–aspartate shuttle?

Pascale

[deustp01]

... would that not be a more appropriate description of the biological purpose of the malate–aspartate shuttle?

The way we used to explain the process to medical students is that, as a result of glycolysis NADH accumulates in the cytosol where it can't be used for much (mostly only NADPH can be be used for biosyntheses and there's no easy way to convert cytosolic NADH to NADPH) and meanwhile the pool of NAD+ needed for continued glycolysis is depleted. The shuttle transfers NADH to the mitochondrion where it can be fed into mitochondrial oxidative phosphorylation, yielding much useful energy, coupled to the restoration of cytosolic NAD+ via the molecular interconversions of the shuttle. So if it is regeneration of anything, it would be NAD+ regeneration, but if there is some sort of NAD(H) homoeostasis term, that would be a better fit to the idea that the whole process works to maintain appropriate levels of NAD and NADH in various cellular compartments. Sanity check, @sjm41

[ValWood]

@sjm41 @rozaru did #28982
make this ticket obsolete?
Do you agree that the matale aspartate shuttle supports the respiratory transport chain, but isn't part of it? of do you think the relationship should be part_of?